An inactivating mutation in the histone deacetylase SIRT6 causes human perinatal lethality.

ABSTRACT: It has been well established that histone and DNA modifications are critical to maintaining the equilibrium between pluripotency and differentiation during early embryogenesis. Mutations in key regulators of DNA methylation have shown that the balance between gene regulation and function is critical during neural development in early years of life. However, there have been no identified cases linking epigenetic regulators to aberrant human development and fetal demise. Here, we demonstrate that a homozygous inactivating mutation in the histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses. In vitro, the amino acid change at Asp63 to a histidine results in virtually complete loss of H3K9 deacetylase and demyristoylase functions. Fu

SUBMITTER: Ferrer CM 

PROVIDER: S-EPMC5900711 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature